Field of the Invention
Cancer immunotherapy based on knocking out or attenuating inhibitor of differentiation proteins (ID proteins) to increase the immunogenicity of tumor, neoplastic or cancer cells.
Related Art
Cancer is the leading cause of death in developed countries and the second leading cause of death in developing countries. While localized tumors are often responsive to therapy, patients with unfavorable tumors and high-risk neoplastic diseases, including inoperative tumors, malignant tumors, metastatic tumors, massive tumors, and other tumors resistant to conventional treatment, have dismal survival rates despite multi-modal therapies. Immunotherapy is an attractive alternative therapeutic option as it potentially offers a more specific treatment than conventional therapies. However, to date, immunotherapies in the form of cancer vaccines have held promise but offered little success.
Id proteins, such as Id2, have been previously associated with apoptosis and cancer. Cao, et al., Oncogene: 28(8):1089-98 (2009) indicated that TGF-beta repression of Id2 induced apoptosis in gut epithelial cells. Zhang, et al. Tumori 100(3): 352-7 (2014) reported that upregulation of Id2 antagonized arsenic trioxide-induced antitumor effects in cancer cells. Zhao, et al., Tumour Biol. 36(6): 4189-96 (2015) reported that silencing Id2 promoted apoptosis of glioblastoma cells, which was attributed to effects that Id2 has on tumor cell chemosensitivity. However, prior studies did not report the effects of knocking out or attenuating Id protein expression on the recognition of tumor cells by the immune system.